The 2025 American College of Allergy, Asthma & Immunology (ACAAI; November 6−10, Orlando, Florida, USA) annual meeting showcased emerging therapies and real-world insights across eosinophilic disorders, atopic disease, chronic respiratory conditions, and allergic rhinitis. From late-breaking clinical trial results to observational data, the conference highlighted advances in convenient, effective, and targeted therapies for patients, as well as strategies to optimize long-term disease management.

Several notable late-breaking studies highlighted novel approaches for chronic and acute allergic conditions.

Benralizumab in hypereosinophilic syndrome (HES):

NATRON (NCT04191304) was a 24-week, Phase 3, randomized, double-blind, placebo-controlled study, investigating benralizumab, an anti-IL-5Rα antibody, plus background therapy in patients ≥12 years with HES.¹

In the Phase 3 trial, benralizumab significantly reduced risk of HES flare (HR: 0.35; 95% CI: 0.18, 0.69; p=0.0024), proportion of patients with flares (22.4% vs 45.5%; OR: 0.31; 95% CI: 0.14, 0.69; p=0.0033), and annualized flare rate (0.41 vs 1.23 flares/year; RR: 0.34; 95% CI: 0.18, 0.63; p=0.0008) versus placebo. Hematologic relapse risk was markedly lower (HR: 0.08; 95% CI: 0.03, 0.20; p<0.0001), and fatigue scores improved (LS means difference: –4.72; 95% CI: –7.64, –1.80; p=0.0017) compared to placebo. Safety was consistent with prior studies, with a similar number of patients experiencing adverse events (AEs; 64.2%, 66.7%) and serious AEs (7.5%, 7.6%) across groups.

*Odds Ratio (OR); Hazard Ratio (HR); Least Squares (LS).

Rezpegaldesleukin for atopic dermatitis and asthma:

REZOLVE-AD (NCT06136741) was a randomized, double-blind, placebo-controlled Phase 2b trial investigating rezpegaldesleukin, a treg-inducing therapy, for adults with moderate-to-severe atopic dermatitis.²

At 16 weeks, rezpegaldesleukin 24 μg/kg every 2 weeks significantly improved mean percent change in Eczema Area and Severity Index (EASI; p<0.001), EASI-75 (p<0.001), EASI-90 (p<0.05), Validated Investigator Global Assessment (vIGA-AD) 0/1 (p<0.05), and Numerical Rating Scale Itch (NRS-Itch) response (≥4-point reduction; p<0.01) compared to placebo. Among patients with uncontrolled asthma (n=25), 75% had clinically meaningful improvement in Asthma Control Questionnaire-5 (ACQ-5; ≥0.5 points reduction) score. No new safety signals were observed.

Intranasal epinephrine spray in severe allergic reactions:

The FDA approved intranasal epinephrine spray 2mg, the first needle-free epinephrine option, for the treatment of severe allergic reactions, including anaphylaxis.³ In real-world use among 680 patients, 603 (88.7%) responded to a single 2mg dose (similar to the rate for injectable epinephrine), with 77 patients (11.3%) requiring a second dose. Ease of use was rated highly by healthcare providers (6.6/7) and patients (6.5/7), supporting the role of intranasal epinephrine spray as a needle-free alternative for severe allergic reactions.

Emerging biologics and targeted therapies continue to show early and sustained benefits in chronic respiratory diseases.

Dupilumab in chronic obstructive pulmonary disease (COPD):

The BOREAS (NCT03930732) and NOTUS (NCT04456673) phase 3, randomized, placebo-controlled trials, investigated dupilumab, a fully human monoclonal antibody, in COPD.⁴ A post hoc analysis evaluated whether dupilumab-related early lung function improvement correlated with improvements in exacerbation rate, symptom burden and quality-of-life.

Early improvements with dupilumab in post-bronchodilator percent predicted forced expiratory volume in 1 second (ppFEV1) at weeks 2 or 4 correlated with reduced annualized moderate exacerbation rates (r=−0.0945; p=0.0042 or r=−0.1043; p=0.0017) and improved 52-week quality-of-life measures: St. George’s Respiratory Questionnaire (SGRQ: r=–0.1945; p<0.0001 or r=–0.2201; p<0.0001), and Evaluating Respiratory Symptoms in COPD (E-RS:COPD: r=–0.1472; p=0.0002 or r=–0.1543; p<0.0001), while placebo demonstrated significant correlations for SGRQ scores alone (r=–0.1399; p=0.0002 or r=–0.1405; p=0.0002), respectively.

*Pearson correlation coefficient (r)

APG808 for mild-to-moderate asthma:

The safety, pharmacokinetics (PK), and pharmacodynamic effect of APG808, an anti-IL-4Rα with half-life extension, on type-2 inflammatory biomarkers was evaluated in a Phase 1 study in healthy adults and patients with asthma.⁵

At 12 weeks, APG808 was well-tolerated, with mild adverse events. PK modelling predicted a half-life of ~55 days, supporting dosing every 2 months or longer. In patients with asthma, multiple doses led to rapid, near-complete inhibition of pSTAT6 and suppression of fractional exhaled nitric oxide (FeNO), with maximal reduction from baseline of 53%, and maintained >30 ppb reduction from baseline.

Depemokimab in severe asthma:

Depemokimab is an investigational, twice-yearly, monoclonal antibody with high affinity for interleukin-5.⁶ SWIFT-1/2 (NCT04719832/NCT4718103) were 52-week, randomized, double-blind, placebo-controlled Phase 3 studies investigating depemokimab for severe asthma with an eosinophilic phenotype.

Depemokimab demonstrated greater improvements from week 1 to 2 in LS mean change from baseline in morning peak expiratory flow (18.08 L/min [95% CI: 14.16, 22.01]), compared to placebo (9.07 L/min [95% CI: 3.65, 14.48]). At week 51–52, improvements were sustained (23.66 [17.64, 29.67]) versus placebo (7.81 [–0.54, 16.16]). Night time awakenings and daily rescue medication use were reduced from week 1–2 and maintained until week 51–52.

Observational studies from clinical practice provide insights into therapy persistence, switching, and long-term safety.

Biologic switching in severe asthma:

In a retrospective study, biologic treatment persistence and switching patterns were observed in patients with a severe asthma diagnosis and at least 2 prescriptions/injections of a biologic.⁷

Electronic medical record (EMR) data from US-based allergy and asthma clinics showed high persistence on initial biologics: tezepelumab (92%), dupilumab (90%), omalizumab (85%). Among switchers, the most common paths were benralizumab to dupilumab (44% of benralizumab switchers) and omalizumab to dupilumab (38% of omalizumab switchers). Lack of efficacy was the main reason for switching, while side effects, payer challenges, or disease progression were also recorded.

Allergic rhinitis therapies and bone density:

A retrospective chart review assessed the impact of allergic rhinitis therapies (oral and intranasal antihistamines, intranasal corticosteroids, and oral anti-leukotriene medications), on long-term bone density scores in women aged 65–85 with allergic rhinitis and a prescription of at least one allergic rhinitis therapy.⁸

In 108 women using intranasal corticosteroids, antihistamines, montelukast or a combination of therapies for an average duration of 4 years, lumbar T-scores averaged –1.334 vs –1.6 in the age-matched control data (p=0.0272) and femoral neck T-scores averaged –1.85 vs –1.8 (p=0.6604), respectively, suggesting no increased risk of osteoporosis.

ACAAI 2025 highlighted a wave of effective therapies for chronic and acute allergic and respiratory conditions. Clinicians can anticipate advances in biologics, targeted immunotherapies, and needle-free delivery options, supported by both robust clinical trial data and real-world practice insights.

References

1. Ogbogu P, Roufosse F, Akuthota P, et al. Benralizumab For Patients With Hypereosinophilic Syndrome: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial (Natron). Annals of Allergy, Asthma & Immunology. 2025;135(5):S2–S3.
2. Corren J, Lio P, Silverberg J, et al. Rezpegaldesleukin, Novel Treg-Inducing Therapy, Demonstrates Efficacy In Atopic Dermatitis And Asthma In Phase 2b Trial. Annals of Allergy, Asthma & Immunology. 2025;135(5):S4.
3. Casale T, Spergel J, Fleischer D, Tanimoto S. Real World Data On The Effectiveness Of Epinephrine Nasal Spray In Clinical Practice-Update. Annals of Allergy, Asthma & Immunology. 2025;135(5):S2.
4. Franssen F, Hanania N, Roche N, et al. Early Lung Function Improvement With Dupilumab Indicates Long-Term Clinical Improvement In Chronic Obstructive Pulmonary Disease. Annals of Allergy, Asthma & Immunology. 2025;135(5):S43–S44.
5. Kamboj A, Hale C, Winter E, et al. APG808, A Novel Anti-IL-4Ra Antibody With Half-Life Extension Technology: Safety, Pharmacokinetics, And Pharmacodynamics. Annals of Allergy, Asthma & Immunology. 2025;135(5):S45.
6. Katial R, Jacques L, Bird N, et al. Twice-Yearly Depemokimab Improves Peak Expiratory Flow And Rescue Inhaler Use In Patients With Asthma: SWIFT-1/2. Annals of Allergy, Asthma & Immunology. 2025;135(5):S46–S47.
7. Chiarella S, McCann W, McEwen I, et al. Switching Biologics In Severe Asthma: Real-World Insights And Clinical Rationale. Annals of Allergy, Asthma & Immunology. 2025;135(5):S5.
8. Boppana S, Shawareb B, Davita T, et al. Impact Of Allergic Rhinitis Therapies On Long-Term Bone Density. Annals of Allergy, Asthma & Immunology. 2025;135(5):S18–S19.